Antidepressant Paxil in spotlight with new report

The widely used antidepressant Paxil is neither safe nor efficient in treating major depression in teenagers, researchers reported late Wednesday in a re-analysis of a controversial patient trial published in the journal BMJ.

The medicine marketed by British drugmaker GlaxoSmithKline is among a blockbuster class of depression drugs used globally for the past two decades, including the most famous of them, Prozac. The study is the latest in a years-long debate about the drugs’ use in teenagers.

Researchers identified more dangerous side effects associated with the drug, including ideas of suicide, compared with the original article published in 2001 in the Journal of the American Academy of Child and Adolescent Psychiatry. Study authors blamed inadequate and incomplete entry of data for the discrepancy.

“The reporting of the study was misleading and dangerous,” David Healy, professor of psychiatry at Bangor University and one of the authors of the reanalysis, told POLITICO.

A Glaxo spokeswoman said the report showed nothing new, noting the risks are part of the drug’s warning label.

“Importantly, the findings…appear to be in line with the longstanding view that there is an increased risk of suicidality in pediatric and adolescent patients given antidepressants like paroxetine,” she told POLITICO. “This is widely known and clear warnings have been in place on the product label for more than a decade. As such we don’t believe this re-analysis affects patient safety.”

The new look at a study of 275 adolescents is part of a push for publishing abandoned or misreported studies. The so-called restoring invisible and abandoned trials initiative has been launched by BMJ, the Public Library of Science and researchers in 2013.

The EU is now implementing a regulation requiring more reporting of drugmakers’ clinical data, going into full effect next year. Advocates want all trials — past and present — put in the public sphere, but under the regulation the disclosure of past trials will remain voluntary.

Healy said that the purpose of the re-analysis went beyond proving the inefficiency of this specific drug.

“I am not calling for any drugs to be banned but doctors and patients need to be able to see trial data,” he said. “You shouldn’t have to depend on GSK’s view or our view, you should have the opportunity to see it yourself and make up your own mind.”

The report found that the two antidepressants they tested, Paxil and a less widely used one, were not more efficient in treating severe depression in adolescents than the placebos they controlled against.

Healy also said that while the results of the study itself didn’t find the drug to be efficient, GSK promoted its effectiveness in its communication aimed at the general public, including the controversial 2001 article.

The drug is part of a best-selling class of selective serotonin reuptake inhibitors, which are used to treat depression, anxiety, and other mood disorders.

The report is the latest in an ongoing debate over the drug’s use in teenagers.

The U.S. drug regulator called the trial at issue “failed” in 2002.

“On balance, this trial should be considered as a failed trial, in that neither active treatment group showed superiority over placebo by a statistically significant margin,” concluded a clinical review by the U.S. Food and Drug Agency in 2002.

However, the FDA didn’t need to reanalyze the study itself because Glaxo acknowledged it did not prove the drug was effective in young people, Healy said. There was no need to prove a benefit and GSK could gain the go “simply by doing the trial.”

Five years later, the agency proposed that manufacturers of antidepressants should specifically warn about increased suicidal thinking and behavior in 18- to 24-year old patients during initial treatment, including both Paxil and Prozac.

The controversy resurfaced in 2012, when GSK was fined $3 billion by the U.S. Department of Justice for bribing doctors to promote Paxil among other drugs.

Prosecutors claimed the drugmaker had fraudulently claimed the drug’s efficacy and promoted its use in adolescents even though trials showed its ineffectiveness in that age group.

In their comment on the re-analysis’ findings GSK stressed its “commitment to data transparency,” noting that they made data from the original trial available to the team that did the re-analysis.

“This particular trial, which was conducted in the 1990s, was included in detailed reviews carried out many years ago by regulators and by GSK which identified the increased risk. It’s something the medical community and regulators are aware of.”